(E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-ethoxyquinazolin-6-yl)-4-(di methylamino)but-2-enamide having the structure as shown in the formula (II), is a newly developed “tinib” drug for EGFR-mutated non-small cell lung cancer as well as EGFR-mutated and Her2-overexpressed non-small cell lung cancer, and it is named neptinib. The remarkable feature of neptinib and its acceptable salts such as dimaleate, xylenesulfonate and hydrochloride is that it is highly prone to produce a specific impurity A, whose possible structure has been identified as shown in the formula (I):

Taking the main ingredient itself as a control, the relative retention time of impurity A is about 0.50-0.52. More particular, through the study of neptinib and its salt forms and crystal forms, a salt-type active ingredient with a stable crystal form has been identified. When only the active ingredient is present, its properties are relatively stable, and under the influence of various factors or after an accelerated stability test at 40° C. for 6 months, there is no significant change in the content of impurities in the active ingredient. However, when the active ingredient is combined with excipients, its stability tend to lowered, and impurity A emerges very easily which accounts for the largest amount of impurity in the active ingredient.
In order to prevent significant increase in the content of impurity A, through extensively compatibility studies of the active ingredient neptinib or its salt with excipients, the present inventors finally has found a group of compositions with low compatibility risks. Under the condition of strictly controlled storage temperature, the content of impurity A produced in the composition can be controlled within the acceptable limits specified by the relevant technical guidelines. Since the lower storage temperature adds additional cost and requires special management measures for practical use, transportation and storage, in order to achieve convenient storage and transportation of neptinib preparations under relatively less strict conditions, the inventors of the present application further studied the production mechanisms of impurity A and found that based on the above compositions with a low compatibility risk, the addition of acids can inhibit the production of impurity A, thereby better controlling the content of impurity A in the composition.